Drainage devices and methods for use

ABSTRACT

Devices and methods for draining excess lymph fluid are disclosed. The device can be fixed to the blood vessel adjacent to the thoracic duct. The device can have a port for withdrawing lymph fluid exiting the thoracic duct. The device can have a cannula and/or subcutaneous port to draw the lymph fluid away from the thoracic duct and reduce hemostatic pressure in the lymphatic system.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of co-pending InternationalApplication No. PCT/US2010/000073, filed Jan. 12, 2010, which claimspriority to U.S. Provisional Application No. 61/204,893, filed 12 Jan.2009. The entire disclosures of these applications are incorporated byreference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present device and method relate generally to accessing, draining,and monitoring the lymphatic system. This device can be used to treatvolume overload in heart failure, pulmonary edema, after surgicalprocedures and in other disease states in which interstitial volumeremoval or lymphatic sampling are of use.

2. Description of the Related Art

Congestive heart failure affects 5.5 million Americans and is a leadingcause of death in the U.S. Each year, over one million patients arehospitalized for heart failure and 90% of these are diagnosed withvolume overload. Volume overload in patients with heart failure is anacute manifestation of a chronic decrease in cardiac performance suchthat the heart is unable to pump and circulate the volume of bloodreturning from the venous system. As a result, blood accumulates in thepulmonary and peripheral tissues. A common and potentially lifethreatening consequence of decompensated heart failure is pulmonaryedema, which presents as shortness of breath and poor oxygenation, bothindicative of fluid accumulation in lung tissues and small airways. Ifleft untreated, patients are at risk for hypoxic arrest and death.Peripheral swelling and venous distension are also common, although notas life threatening.

In most cases, patients with this presentation are known to be sufferingfrom a chronic heart condition and are taking prescribed diureticmedications to control their volume status. The sudden onset of volumeoverload is due to either a miscalculation in salt and fluid intake orpoor medication compliance on the part of the patient, or a result of aworsening heart condition, renal impairment, or resistance to diureticmedications.

Once diagnosed, the initial therapy for volume overload in decompensatedheart failure is intravenous diuresis. Despite the use of intravenousdiuretics in 90% of overload patients, the average hospital admissiontime is 4.3 days and over half of those discharged will return withinsix (6) months with the same diagnosis. It is suggested that the highreadmission rate is due to inadequate volume reduction during theirprevious admission. Furthermore, approximately 30% of chronic heartfailure patients on diuretics will develop resistance or renal failureas a result of their medication and require more invasive and higherrisk therapies to control their volume status. These interventionsinclude mechanical ventilation with positive pressure, central venousultrafiltration, or hemodialysis.

The physiology of pulmonary edema suggests fluid accumulation in thesmall airways is the direct result of increased hydrostatic pressure inthe surrounding capillaries, which leak first into the interstitialspace between the capillary bed and the airway. This extracellular spaceis composed of protein matrices and small lymphatic channels designedspecifically to accommodate homeostatic changes in pressure by drainingany excess interstitial fluid which is not immediately resorbed by thevenous capillary bed. These lymphatic channels combine as they traveltowards the neck, eventually forming one large channel called thethoracic duct. The thoracic duct rejoins the systemic venous system atthe lymphovenous junction, near the confluence of the left internaljugular and subclavian veins. In the case of clinically significantpulmonary edema, the hydrostatic forces generated by a failing heartquickly overwhelm the lymphatic system and blood plasma overflows intothe smaller airways. In this case, the lymphatic system is limited byvolume capacity and higher than expected flow pressures generated by thevenous system into which the thoracic duct is draining.

The human lymphatic system has been accessed previously for the purposesof sampling and draining lymphatic fluid to treat blood cancers,transplant rejection, pancreatitis and rheumatoid arthritis. Thesemaneuvers have involved open surgery and acute cannulation of thethoracic duct in small numbers of patients with extracorporealprocessing of lymphatic fluid. The majority of the fluid was returned tothe patient after processing.

While the function and overloading of the lymphatic system in pulmonaryedema is well documented, current therapies for volume overload focus onsystemic pharmaceutical diuresis or direct drainage of the vascularcompartment to filter and remove blood plasma. Therefore, there exists aneed for a therapy to monitor and manage pulmonary and systemic volumeoverload by manipulation and drainage of the existing lymphatic system.Drainage of lymphatic fluid specifically from the thoracic duct canquickly reverse the interstitial fluid imbalance in the pulmonarytissues and offload a significant amount of peripheral volume.Furthermore, lymphatic fluid is pre-filtered and does not include redblood cells or platelets which need to be separated and returned to thepatient in conventional hemodialysis and ultrafiltration.

Outside of heart failure, development of this device will provide a muchneeded tool to accelerate research and treatment in a range of relateddisease states such as cancer, HIV, organ transplant, and autoimmunedisorders.

Interstitial fluid accumulation can become a critical issue in anypost-operative patient and is especially concerning after heart surgery,when it is important to limit cardiac stress. In these critical care andpost-surgical volume management situations, and at other times, thoracicduct drainage in at-risk patients can augment volume management andprevent overload.

Fluid in the thoracic duct contains a high percentage of circulatingCD-4 lymphocytes, the target cell for HIV. In animal models, drainageand characterization of T-cells by thoracic duct drainage can answersome of the fundamental immunological questions about recirculatinglymphocyte pools to help develop new vaccine and antiviral therapies.

An early method of immune suppression in organ transplantation wasthoracic duct drainage. The open cannulation procedure and subsequentwound care was challenging and unsuccessful in many patients. Onceimmune suppressive medications became more effective, this approach wasabandoned altogether.

SUMMARY OF THE INVENTION

The devices and methods described herein can enable repeated fluidcommunication between an internal body vessel and an extracorporealfluid reservoir, such as a syringe. In one embodiment, the device canhave a cannula or other tubular member. The cannula can enable fluidcommunication between the vessel and an external accessing device. Thedevice can be in fluid communication with the vessel with or withoutoccluding the vessel. If fluid is not being withdrawn from the cannula,the fluid in the body vessel can bypass the cannula. The device canremain in a fixed position in the vessel. The device can be securedinternally, externally, or a combination thereof, to the body vessel.The cannula can be secured along the internal lumen of the body vesselby stabilizing members. The stabilizing members can support the vessel.The stabilizing members can be a single balloon, for example, positionedat the junction of the thoracic duct and the innominate vein, or twoballoons, for example positioned on opposite sides of the thoracic ductport as the thoracic duct merges into the innominate vein. Thestabilizing members can include anchoring hooks and/or loops. Thedevice, such as on the outer perimeter of the balloon, can have aningrowth matrix to promote endothelial growth into the device to fix thedevice to the surrounding tissue, such as the vessel wall.

The device can be anchored in and/or to the vessel without occluding thevessel, for example, even in very small vessels. The device can be ableto puncture the vessel wall. The cannula can create the path for fluidflow external to the vessel and/or a means to access the vessel. Thedevice can include an access port. The device can include a pressuresensor. The device can include valves to control fluid flow. The devicecan include a reservoir to hold fluid that has traveled through thecannula.

The device may be used to remove lymphatic fluid in patientsexperiencing pulmonary edema. When the patient is not experiencingpulmonary edema, for example, the lymphatic fluid may flow through thevessel past the cannula. When the patient is experiencing higher thannormal flow of lymphatic fluid, for example, the fluid may activate anentrance mechanism to the cannula and/or signal that the device needs tobe accessed. When the device is accessed, fluid may be withdrawn fromthe lumen through the cannula. When the patient is experiencingpulmonary edema or at the onset of pulmonary edema, the device may beaccessed.

The device can allow fluid communication between a lymphatic vessel andan external reservoir. For example, the device can open the wall of(i.e., access) the thoracic duct. The device can drain fluid from thelymphatic vessel. For example, the cannula can drain fluid from thethoracic duct. The device can drain lymphatic fluid from the lymphaticsystem, for example, when the patient becomes fluid-overloaded orsuffers from congestive heart failure. The device can help preventand/or treat congestive heart failure and pulmonary edema, for example,by drainage of the lymphatic system.

The device may access blood vessels. The device may access centralvenous or arterial vessels. The device may withdraw fluid from thevessels. The device may withdraw blood from blood vessels. The devicemay store the fluid in a reservoir. The device may access the portalvein. The device may access the proximal portal vein, before the triad.The device may measure the pressure in blood vessels. The device maymeasure portal hypertension.

The device can be placed in a stationary fashion in a blood vesseladjacent to the thoracic duct. The device can have a port positionedadjacent to the opening of the thoracic duct into the innominate,internal jugular or subclavian vein or the junction thereof. The devicecan be used to passively or actively (e.g., by applying negativepressure) withdraw lymphatic fluid as it exits the thoracic duct intothe adjacent vein. The device's port, which is adjacent to the thoracicduct, can be in fluid communication with a drainage cannula and/orsubcutaneous port that can be used to withdraw the lymph fluid.

The device can be deployed adjacent to the opening of the thoracic ductinto the innominate vein. The device can be deployed in a minimallyinvasive fashion, such as through a subclavian or other intravasculardelivery. The thoracic duct opening can be identified using avisualization method. For example, the thoracic duct opening can beidentified using an intra-venous ultrasound (IVUS) probe. The IVUS probecan be in a liquid-inflatable (e.g., saline) balloon. The thoracic ductopening can be identified using a sensor to identify changes in theintravascular fluid composition. For example, lymph fluid is typicallymore alkaline than blood, so a pH sensor can be deployed into theinnominate vein to locate the peak pH when in the vicinity of thethoracic duct to locate the opening of the thoracic duct into theinnominate vein. A combination of methods, such as those disclosedherein, can be used to identify the thoracic duct opening to coordinateplacement of the device.

A user may singularly or repeatedly access the device, for example, tosample lymph fluid for monitoring of triglycerides, lymphocytes, orlymphatic protein content in chronic conditions such as hyperlipidemia,cancer, immune deficiencies or auto-immune disorders.

A user may singularly or repeatedly access the device, for example, tosample lymph fluid and/or for reduction of fluid volume in patientsexperiencing or at risk for volume overload, and/or pulmonary edemaand/or chronic heart failure and/or acute exacerbation of chronic heartfailure.

Periodic monitoring of lymphocyte antigen, for example, after solidorgan transplant, can provide an early warning of graft rejection and amore accurate indication of the level of immune suppression. Forexample, lymph fluid can be withdrawn through the device and analyzedafter a high risk graft or transplant procedure. For example, the devicecan be implanted and lymph fluid can be removed through the device andanalyzed for graft rejection after a heart, lung, kidney, skin, liver,or small intestine transplant or graft. The device can provide a safeand minimally invasive method of lymphatic access, which could beprovided with a transcutaneous catheter. Routine drainage of sensitizedlymphocyte subpopulations could help prevent or rescue an acute episodeof rejection.

As a clinical modality, catheter drainage of the thoracic duct throughthe device can remove the lymph fluid to deplete large numbers of CD-4cells (for example, CD-4⁺ T cells). Combining drainage with conventionalpharmacological therapy to decrease the infection rate in remaining CD-4cells can promote a shift towards a virus-free state and represents anintriguing alternative to current treatment for HIV or other infectiousdiseases with similar modalities.

In accordance with another embodiment, a method is provided for reducinginterstitial volume in a patient using a device comprising a tubularmember that includes placing a distal end of the tubular member into apatient's venous system such that the distal end is located adjacent thethoracic duct; draining fluid from the lymphatic system via the thoracicduct through a lumen of the tubular member to reduce fluid volume withinthe patient's body; and discontinuing draining fluid when the fluidvolume is sufficiently reduced.

Optionally, the method may also include resuming draining fluid from thelymphatic system via the thoracic duct when the pressure in the thoracicduct exceeds a predetermined threshold, e.g., about twenty fivemillimeters of Mercury pressure (25 mm Hg).

In accordance with yet another embodiment, a method is provided fordecreasing lymphocyte numbers in a patient affected by autoimmune orinfectious disease using a device comprising a tubular member thatincludes placing a distal end of the tubular member into a patient'svenous system such that the distal end is located adjacent the thoracicduct; and draining fluid from the lymphatic system via the thoracic ductthrough a lumen of the tubular member.

Optionally, the method may also include analyzing lymphocytes in thefluid drained from the thoracic duct to identify a subset oflymphocytes; removing the identified subset of lymphocytes from thefluid; and returning the fluid into the patient's body after removingthe identified subset of lymphocytes. In another option, the method mayinclude analyzing lymphocytes in the fluid drained from the thoracicduct; processing the fluid outside the patient's body; and returning thefluid into the patient's body.

In accordance with still another embodiment, a method is provided forevaluating interstitial fluid status within a patient's body thatincludes placing a distal end of a tubular member into a patient'svenous system such that the distal end is located adjacent the thoracicduct; measuring pressure within the tubular member distal end toapproximate lymphatic pressure within the thoracic duct; providing analert outside the patient's body when the measured pressure within thetubular member exceeds a predetermined threshold; and removinginterstitial fluid from the thoracic duct via the tubular member untilthe measured pressure falls below the predetermined threshold.

For example, the methods herein may include substantially isolating thethoracic duct from the venous system using the device such that flowfrom the thoracic duct is directed through the tubular member to drainfluid from the lymphatic system.

In one embodiment, the distal end of the tubular member may beintroduced into the venous system until the distal end is advanced intothe thoracic duct. Optionally, negative pressure may be applied to thelumen to increase fluid flow from the thoracic duct through the cannula.

In another embodiment, the device may include a subcutaneous access portcoupled to the tubular member for accessing fluid drained through thetubular member.

In addition or alternatively, the device may include one or moreballoons on the tubular member, and the method may include inflating theone or more balloons to maintain the tubular member in a substantiallyfixed position relative to the thoracic duct.

In yet another embodiment, the device may include a Nitinol frame, andthe method may include expanding the frame to maintain the tubularmember in a substantially fixed position relative to the thoracic duct.For example, the device may include an elastic material on the Nitinolframe, e.g., a silicone component, to substantially isolate the thoracicduct from the venous system and maintain the tubular member in asubstantially fixed position relative to the thoracic duct.

In accordance with yet another embodiment, a device is provided foraccessing fluid from a thoracic duct of a patient via the patient'svenous system that includes a tubular member comprising a distal endsized for introduction into the patient's venous system adjacent thethoracic duct; one or more features on the distal end for substantiallyisolating the thoracic duct from the venous system; and a lumen forwithdrawing interstitial fluid from the thoracic duct. For example, thedistal end is sized to fit inside the subclavian vein of the patient,and wherein the tubular member has a length sufficient to extend to thethoracic duct from a percutaneous access point in the left subclavianvein.

In one embodiment, the one or more features may include a Nitinol frameand a low durometer silicone component or other elastic member includingan opening communicating with the lumen. For example, the Nitinol framemay include two flexible members extending from the tubular member andsupporting the silicone component. Optionally, the silicone componentmay be bonded to the Nitinol frame, the silicone component beingsufficiently flexible to stretch to substantially seal the thoracic ductoutlet.

Other aspects and features of the present invention will become apparentfrom consideration of the following description taken in conjunctionwith the accompanying drawings.

SUMMARY OF THE DRAWINGS

It will be appreciated that the exemplary apparatus shown in thedrawings are not necessarily drawn to scale, with emphasis instead beingplaced on illustrating the various aspects and features of theillustrated embodiments.

FIG. 1A illustrates the major venous anatomy of the chest and neck andthe location of the thoracic duct.

FIG. 1B illustrates the location of the thoracic duct outlet as itenters the central venous system.

FIG. 2A illustrates a variation of the drainage device placed in thethoracic duct with a subcutaneous port under the skin of the left chestwall.

FIG. 2B illustrates a variation of the drainage device in deployed in athoracic duct.

FIG. 2C illustrates a variation of a subcutaneous port and in-linesensor.

FIG. 3A illustrates a variation of the drainage device in which theintraluminal member has the shape of a closed cylinder.

FIG. 3A′ illustrates a variation of the drainage device in which theintraluminal member has the shape of a hemi-cylinder.

FIG. 3B illustrates a variation of the device deployed in a thoracicduct in which the intraluminal member has the shape of an incompletecylinder.

FIG. 3B′ illustrates a variation of the device of FIG. 3B.

FIGS. 4A through 4D illustrate a variation of a method for delivery of atwo-piece intra-ductal device.

FIGS. 5A through 5C illustrate a variation of a method for delivery of aone-piece intra-ductal device.

FIG. 6A illustrates a variation of the device deployed in the centralvenous system in opposition to the thoracic duct outlet.

FIG. 6B is an end view of the device of FIG. 6A.

FIG. 6C is a close-up of the distal end of the device of FIG. 6A.

FIG. 7 illustrates a variation of the device deployed in the centralvenous system in opposition to the thoracic duct outlet.

FIGS. 8A through 8C illustrate a variation of a method for delivery of avariation of the device into the central venous system usingintravascular ultrasound guidance.

DETAILED DESCRIPTION

The devices and methods disclosed herein enable removal of fluid from avessel within the body. For example, the device can be placed in a lymphor blood vessel to remove lymph fluid from the body. The removal oflymph fluid can reduce the hemostatic pressure in the lymphatic system,reducing symptoms of congestive heart failure.

The device can access the lumen of a body vessel, for example, alymphatic vessel and/or blood vessel. Fluid can drain from the vesselinto the device. For example, the device can be in fluid communicationwith the thoracic duct or central veins (e.g., subclavian vein, internaljugular vein, superior vena cava, and innominate vein) shown in FIG. 1Aand FIG. 1B. The device can reduce the pressure within the lumen bydraining and removing excess fluid. The excess fluid can be stored inthe device. The excess fluid can flow through a port and removedpercutaneously. The device could treat pulmonary edema, for example, byreducing the pressure in the interstitial space, such as around thealveoli.

The device can have a cannula, intraluminal and extraluminal members,and one or more of the following: access port, sensor, pressure sensor,flow meter, reservoir.

Fluid overload, or hypervolemia, is a medical condition where there istoo much fluid in the blood. The total body fluid can be too much forthe heart to pump. Under normal physiological conditions, this wouldresult in fluid building up in the tissue. The thoracic duct outletwould typically allow lymph fluid to drain from the thoracic duct intocentral venous system, but when the blood pressure in the innominatevein becomes too high compared to the lymph fluid pressure in thethoracic duct, the lymph fluid cannot properly drain through thethoracic duct outlet and may prevent proper draining of the lymph systemand exit the lymphatic system in a pathological manner.

FIG. 2A illustrates a variation of the drainage device placed inside thethoracic duct. The draining device can be in fluid communication with atube or cannula. The drainage device can be connected to and in fluidcommunication with a subcutaneous port, for example, via the cannula.The drainage device can be placed anywhere along the cervical thoracicduct. The cannula can drain fluid from the draining device to aninternal or external reservoir or port, such as the subcutaneous port.The subcutaneous port can be drained, for example, by occasional accessby a percutaneous needle.

FIG. 2B illustrates that the drainage device may include intraluminaland extraluminal members. The intraluminal and/or extraluminal memberscan be cylindrical and/or conical in shape.

The intraluminal member of the device can be inserted into the thoracicduct lumen. The intraluminal member can be hollow. The intraluminalmember can be in fluid communication with the body lumen, for example,the thoracic duct. The intraluminal member can be capable of carryingfluid from the body lumen. The intraluminal member can be in continuousor discontinuous (i.e., temporary, or sequentially repeating off and onby automatic or manual control) fluid communication with the body lumen.The cannula can access the vessel without significantly occluding thevessel. The intraluminal member can occupy some of the cross sectionalarea of the vessel the intraluminal member is accessing. Theintraluminal member can occupy a small amount of the cross sectionalarea of the blood vessel. The extraluminal member of the device can bein fluid communication with both the intraluminal member and thecannula. The extraluminal member can cross the full thickness of thethoracic duct wall.

The drainage device can remain in a given position in the vessel byhooks and barbs (not shown). The drainage device can maintain theposition without hooks and barbs. The extraluminal member may be securedto the cannula. The cannula can hold the drainage device in place. Theexterior surface of the drainage device, such as along the intraluminalmember, can have an ingrowth matrix configured to promote tissueingrowth to anchor the drainage device to the surrounding tissue, suchas the endothelium or intima of the blood vessel.

The intraluminal and extraluminal members may be rigid. The intraluminaland extraluminal members may be flexible. The intraluminal and/orextraluminal members can have soft grafts and/or reinforcingself-expandable or balloon-expandable metal or polymer stents. Portionsof the intraluminal or extraluminal members may be more rigid, forexample, the extraluminal member. Portions of the intraluminal orextraluminal members may be more flexible, for example, the intraluminalmember.

The device can enable indirect access to the vessel. The device can beaccessed by a needle on a syringe, and the device can include an accessport. The access port can be in fluid communication with the vessel. Theaccess port can be connected to the cannula and the cannula can be influid communication with the vessel.

FIG. 2C illustrates that the access port can be a subcutaneous accessport. The access port may include a gel port. The gel port can beself-sealing, for example, re-sealing after removal of the accessdevice, such as a needle. The access port may be in fluid communicationwith the cannula.

The device may include one or more sensors. The sensors may includepressure sensors, pH sensors, ultrasound sensors, and/or volume sensors.The sensors may detect temperature and/or changes in temperature and/orimpedance and/or changes in impedance and/or chemical composition of thefluid (such as acidity and alkalinity) and/or changes in chemicalcomposition of the fluid. The sensors may detect pressure and/or changesin pressure in the vessel and/or in the cannula and/or in the device.The sensors may detect flow volume and/or changes in flow volume in thecannula and/or in the vessel and/or in the device. FIG. 2C shows that asensor may be connected to the cannula between the intraluminal memberand the subcutaneous access port. The sensor may be in fluidcommunication with the vessel, for example the thoracic duct.

The sensor may have a means to signal the patient to high pressure. Thesensor may signal when drainage of fluid is necessary. For example, thesensor may be in communication with an external device. The sensor maysignal the external device. The external device may notify the patient.

The sensor may enable a physical deformation of some component of thedevice at a specified threshold. For example, the sensor may be apressure sensor. The pressure sensor may be comprised of a valve and achamber. The valve may allow fluid to pass into a reservoir only at acertain pressure. The reservoir may expand when it has fluid. Theexpansion may be detectable by the patient and/or by physical exam.

FIG. 3A shows that the intraluminal member can be tubular orcylindrical. FIG. 3A′ illustrates that the intraluminal member can havea semi-cylindrical or partially tubular structure where the halves ofthe tube, as measured from the center of the base of the cannula, areidentical. When implanted in a vessel, the intraluminal member canpromote laminar flow through the vessel. The intraluminal member canhave a smooth surface, for example on the surface facing the vessel intowhich the member is implanted. The intraluminal member can aid in flowof fluid through the vessel.

FIGS. 3B and 3B′ illustrate that the intraluminal member can be or havea self-expanding (i.e., elastically deformable) or balloon-expanding(i.e., plastically deformable) metal, plastic, or biodegradablewireframe or stent.

The device may be delivered to a vessel lumen over guidewires inseparate parts. Some or all members may be expandable. Some or allmembers may have two configurations.

A guidewire may be used to help place the device. The guidewire may beinserted trans-abdominally. The guidewire may be advanced into thelymphatic system. The guidewire may be advanced up the lymphatic system,with the flow of lymphatic fluid, towards the thoracic duct. The same ora second guidewire may puncture the thoracic duct. The guidewire may beadvanced towards the skin. An incision may be made in the chest. Theincision may be made until the guidewire is able to be advanced to theskin. The cannula and/or an access port may be loaded on the guidewire.The access port may be inserted into the body and connected to thecannula.

FIGS. 4A through 4D illustrate that the device can be implanted in thethoracic duct. FIG. 4A illustrates that the device may be placed over aguidewire. The guidewire could be placed from the proximal lymphaticsystem using standard interventional radiology techniques. For example,the guidewire could be placed trans-abdominally. The cysterna chylicould be cannulated and a guidewire could be advanced in the lymphaticsystem. The guidewire could be advanced until it is at the thoracicduct. The cannula may be expanded once in the desired position. Thecannula may be expanded in the thoracic duct. As another example, avein, such as the internal jugular vein, could be cannulated with ahollow needle. The guidewire could be advanced into the junction of thethoracic duct to the venous system, then into the lymphatic system. Thiscould be achieved with a curved-tip wire. Once in the correct position,the device could be deployed. Once the device is in the correct positionthe device could be expanded. The device could be expanded using aballoon, for example.

FIG. 4A shows that the intraluminal member may have a compressedconfiguration. The intraluminal member can be delivered over a guidewirefrom the distal end of the vessel. FIG. 4B shows that the intraluminalmember may have a second, expanded configuration. The intraluminalmember may have an aperture in its expanded formation for inserting andconnecting the extraluminal member. FIG. 4C shows the extraluminalmember can be delivered in a compressed configuration over a guidewirefrom the distal vessel. The guidewire can be passed through the exithole in the intraluminal member. The extraluminal member can be passedthrough the exit hole in the intraluminal member over the guidewire.FIG. 4D shows that the extraluminal member can be expanded and connectedto the intraluminal member. The cannula may be connected to thestabilizing members after implantation.

FIGS. 5A through 5C illustrate that the cannula and the stabilizingmembers can be part of a unitary body. The cannula and the stabilizingmembers can all be part of a unitary body with no seams betweencomponents.

FIG. 5A illustrates that the device can be delivered over a guidewire tothe target vessel as a unitary body. In FIG. 5A, the device can bedelivered to the vessel from a proximal location outside the vessel. InFIGS. 5B and 5C, the device can be radially expanded once the device hasbeen positioned inside the thoracic duct.

The device and/or the access points to the vessel can be detectableusing a visualization technology, for example ultrasound. Fluid from thevessel can be withdrawn through the drainage device by another device,for example, a needle.

The drainage device can be accessed by any number of other devices. Theaccessing devices may be capable of transporting fluid, and/or measuringpressure. For example, access can entail percutaneous cannulation of thedevice by a needle. Access can include access of the cannula and/oraccess of another member of the device. For example, access can includepercutaneous cannulation of a subcutaneous access port of the device.

The cannula connected to the drainage device may include one or morevalves. The valves may be pressure activated. For example, fluidpressure in the vessel lumen may open the valve. Fluid flow above normalphysiological flow can open the valve. Once open, fluid can flow up thecannula. This may signal the patient. The signal may be physical. Forexample, the fluid may cause the access port to deform in a way that isdetectable to the patient. The device can have a valve in the cannulathat controls access to a reservoir. The valve may selectively open whenthe pressure of the lymphatic fluid reaches above the normalphysiological pressure of the specific patient. The valve can be aone-way valve, such that fluid may never flow back to the vessel. Thevalve can be a pressure valve as fluid goes from the vessel towards thetip of the cannula, but allows free flow from the tip of the cannulaback towards the base of the cannula. The device may be removable. Thedevice may be collapsible. The components may have joints. For example,the tubular stabilizing members can be magnetic, and deform if amagnetic tube is placed at the core, along the longitudinal axis. Thedevice can be collapsed under vacuum pressure. The device can becollapsed and removed. Use of the device and/or draining the lymphaticsystem can be used as a step to reverse and/or treat pulmonary edemaand/or volume overload and/or acute heart failure and/or chronic heartfailure and/or acute exacerbation of chronic heart failure.

Access can include acute cannulation and/or a means to leave behind animplanted device. Access may include trans-venous access, which mayinclude trans-jugular, subclavian and/or femoral. Access may includeaccess through soft tissue, which may include transcutaneous, whichcould include abdominal access and/or access through thoracic structuresand/or access by way of and/or through nuchal structure.

Access may be aided by imaging modalities. Imaging modalities mayinclude ultrasound, fluoroscopy, x-ray, magnetic resonance, computedtomography, direct vision, and/or magnified vision.

The lymphatic system may include the thoracic duct, and/or cisternachyli and/or any vessel that carries the fluid and/or all vessels thatcarry the fluid.

Removal of the fluid may include draining the fluid to a reservoirinside and/or outside the body. A reservoir inside the body may includeanother area of the body, whether or not it is a cavity (i.e., thearms). A reservoir outside the body may include a container and/or anunenclosed area, draining the fluid to a naturally occurring and/orman-made container. Draining may be by way of continuous drainage and/orintermittent drainage, for example, draining can be activated when thepressure in the thoracic duct exceeds a predetermined amount. Suchdrainage can be by way of implanting a valve at the distal end of thethoracic duct; and/or by way of accessing a port; and/or by way ofapplying a mechanical force to the duct and/or to a lymphatic vesseland/or to the lymphatic system; and/or by way of cannulating the ductand/or a lymphatic vessel. The port can be permanently implanted.

The device may be accessed, for example, by a needle. Fluid may bewithdrawn from the interior lumen, through the device. The overall fluidvolume of the patient may be reduced.

The device may reside in the central venous system. The device mayocclude or cover the outlet of the thoracic duct in the central venoussystem. The device may seal permanently or temporarily against theoutlet of the thoracic duct. The device can fluidly isolate the thoracicduct outlet port from the venous system. For example, the distal balloonand proximal balloon can be positioned on opposite sides of the thoracicduct outlet port, and the lymph collection port (e.g., an aperture orvalve on in fluid communication with the lymph drainage cannula) can beplaced adjacent to the thoracic duct outlet port. The device may beactivated to seal against the thoracic duct outlet only when drainage isrequired. FIG. 6A illustrates a variation of the device which sealsagainst the thoracic duct using inflatable balloons. The device mayallow for venous blood to pass through it when the balloons areinflated. FIG. 6B illustrates the pass-through lumen of the inflatedballoons.

The device in the central venous system may be comprised of aself-expanding metallic structure. The structure may be assembled fromone piece or multiple parts. The device may be delivered to the centralvenous system over a guidewire. FIG. 7 illustrates a self-expandingcentral venous device deployed in opposition to the thoracic ductoutlet. The device can have self-expanding Nitinol struts and braces.

FIG. 8 illustrates delivering a central venous device with inflatableballoons over a guidewire. The location where the device will bedeployed may be determined using an intravascular imaging modality, suchas intravascular ultrasound. In FIG. 8A, an intravascular ultrasoundprobe can used to locate the thoracic duct outlet from the internaljugular vein. Once the location of the outlet has been determined, theintravascular ultrasound probe is removed and the balloon catheter isdeployed as depicted in FIG. 8B. In FIG. 8C, the balloon catheter can beexpanded in place to cover the outlet of the thoracic duct. Lymphaticfluid can be withdrawn from the cannula.

The device may be implanted. The implantation may be using a minimallyinvasive technique, for example, those techniques commonly used byinterventional radiologists and/or interventional cardiologists. Thedevice may enter the body at a point in the vessel more distal to thedesired position. For example, the device may enter trans-abdominallyinto the cysterna chyli. The device may be manipulated through thevessel. Visualization aids may aid in advancing the device and/or aguidewire. For example, fluoroscopy may be used. Mechanical aids can beused to advance the device and/or a guidewire. Once in the desiredposition, the vessel may be punctured. Using such a technique, thecomplications associated with open surgery can be avoided.

Any or all elements of the device and/or other devices or apparatusdescribed herein can be made from, for example, a single or multiplestainless steel alloys, nickel titanium alloys (e.g., Nitinol),cobalt-chrome alloys (e.g., ELGILOY® from Elgin Specialty Metals, Elgin,Ill.; CONICHROME® from Carpenter Metals Corp., Wyomissing, Pa.),nickel-cobalt alloys (e.g., MP35N® from Magellan Industrial TradingCompany, Inc., Westport, Conn.), molybdenum alloys (e.g., molybdenum TZMalloy, for example as disclosed in International Pub. No. WO 03/082363A2, published 9 Oct. 2003, which is herein incorporated by reference inits entirety), tungsten-rhenium alloys, for example, as disclosed inInternational Pub. No. WO 03/082363, polymers such as polyethyleneteraphathalate (PET), polyester (e.g., DACRON® from E. I. Du Pont deNemours and Company, Wilmington, Del.), poly ester amide (PEA),polypropylene, aromatic polyesters, such as liquid crystal polymers(e.g., Vectran, from Kuraray Co., Ltd., Tokyo, Japan), ultra highmolecular weight polyethylene (i.e., extended chain, high-modulus orhigh-performance polyethylene) fiber and/or yarn (e.g., SPECTRA® Fiberand SPECTRA® Guard, from Honeywell International, Inc., Morris Township,N.J., or DYNEEMA® from Royal DSM N.V., Heerlen, the Netherlands),polytetrafluoroethylene (PTFE), expanded PTFE (ePTFE), polyether ketone(PEK), polyether ether ketone (PEEK), poly ether ketone ketone (PEKK)(also poly aryl ether ketone ketone), nylon, polyether-blockco-polyamide polymers (e.g., PEBAX® from ATOFINA, Paris, France),aliphatic polyether polyurethanes (e.g., TECOFLEX® from ThermedicsPolymer Products, Wilmington, Mass.), polyvinyl chloride (PVC),polyurethane, thermoplastic, fluorinated ethylene propylene (FEP),absorbable or resorbable polymers such as polyglycolic acid (PGA),poly-L-glycolic acid (PLGA), polylactic acid (PLA), poly-L-lactic acid(PLLA), polycaprolactone (PCL), polyethyl acrylate (PEA), polydioxanone(PDS), and pseudo-polyamino tyrosine-based acids, extruded collagen,silicone, zinc, echogenic, radioactive, radiopaque materials, abiomaterial (e.g., cadaver tissue, collagen, allograft, autograft,xenograft, bone cement, morselized bone, osteogenic powder, beads ofbone) any of the other materials listed herein or combinations thereof.Examples of radiopaque materials are barium sulfate, zinc oxide,titanium, stainless steel, nickel-titanium alloys, tantalum, and gold.

Any or all elements of the device and/or other devices or apparatusdescribed herein, can be, have, and/or be completely or partially coatedwith agents and/or a matrix a matrix for cell ingrowth or used with afabric, for example, a covering (not shown) that acts as a matrix forcell ingrowth. The matrix and/or fabric can be, for example, polyester(e.g., DACRON® from E. I. Du Pont de Nemours and Company, Wilmington,Del.), poly ester amide (PEA), polypropylene, PTFE, ePTFE, nylon,extruded collagen, silicone, any other material disclosed herein, orcombinations thereof.

The device and/or elements of the device and/or other devices orapparatus described herein and/or the fabric can be filled, coated,layered, and/or otherwise made with and/or from cements, fillers, glues,and/or an agent delivery matrix known to one having ordinary skill inthe art and/or a therapeutic and/or diagnostic agent. Any of thesecements and/or fillers and/or glues can be osteogenic and osteoinductivegrowth factors.

Examples of such cements and/or fillers includes bone chips,demineralized bone matrix (DBM), calcium sulfate, corallinehydroxyapatite, biocoral, tricalcium phosphate, calcium phosphate,polymethyl methacrylate (PMMA), biodegradable ceramics, bioactiveglasses, hyaluronic acid, lactoferrin, bone morphogenic proteins (BMPs)such as recombinant human bone morphogenetic proteins (rhBMPs), othermaterials described herein, or combinations thereof.

The agents within these matrices can include any agent disclosed hereinor combinations thereof, including radioactive materials; radiopaquematerials; cytogenic agents; cytotoxic agents; cytostatic agents;thrombogenic agents, for example, polyurethane, cellulose acetatepolymer mixed with bismuth trioxide, and ethylene vinyl alcohol;lubricious, hydrophilic materials; phosphor cholene; anti-inflammatoryagents, for example, non-steroidal anti-inflammatories (NSAIDs) such ascyclooxygenase-1 (COX-1) inhibitors (e.g., acetylsalicylic acid, forexample, ASPIRIN° from Bayer AG, Leverkusen, Germany; ibuprofen, forexample, ADVIL® from Wyeth, Collegeville, Pa.; indomethacin; mefenamicacid), COX-2 inhibitors (e.g., VIOXX® from Merck & Co., Inc., WhitehouseStation, N.J.; CELEBREX® from Pharmacia Corp., Peapack, N.J.; COX-1inhibitors); immunosuppressive agents, for example, Sirolimus(RAPAMUNE®, from Wyeth, Collegeville, Pa.), or matrix metalloproteinase(MMP) inhibitors (e.g., tetracycline and tetracycline derivatives) thatact early within the pathways of an inflammatory response. Examples ofother agents are provided in Walton et al, Inhibition of ProstoglandinE₂ Synthesis in Abdominal Aortic Aneurysms, Circulation, Jul. 6, 1999,48-54; Tambiah et al, Provocation of Experimental Aortic InflammationMediators and Chlamydia Pneumoniae, Brit. J. Surgery 88 (7), 935-940;Franklin et al, Uptake of Tetracycline by Aortic Aneurysm Wall and ItsEffect on Inflammation and Proteolysis, Brit. J. Surgery 86 (6),771-775; Xu et al, Sp1 Increases Expression of Cyclooxygenase-2 inHypoxic Vascular Endothelium, J. Biological Chemistry 275 (32)24583-24589; and Pyo et al, Targeted Gene Disruption of MatrixMetalloproteinase-9 (Gelatinase B) Suppresses Development ofExperimental Abdominal Aortic Aneurysms, J. Clinical Investigation 105(11), 1641-1649 which are all incorporated by reference in theirentireties.

Any elements described herein as singular can be pluralized (i.e.,anything described as “one” can be more than one). Any species elementof a genus element can have the characteristics or elements of any otherspecies element of that genus. The above-described configurations,elements, or complete assemblies and methods and their elements forcarrying out the invention, and variations of aspects of the inventioncan be combined and modified with each other in any combination.

While the invention is susceptible to various modifications, andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that the invention is not to be limited to the particular formsor methods disclosed, but to the contrary, the invention is to cover allmodifications, equivalents and alternatives falling within the scope ofthe appended claims.

1. A method for reducing interstitial volume in a patient using a devicecomprising a tubular member, the method comprising: placing a distal endof the tubular member into a patient's venous system such that thedistal end is located adjacent the thoracic duct; draining fluid fromthe lymphatic system via the thoracic duct through a lumen of thetubular member to reduce fluid volume within the patient's body; anddiscontinuing draining fluid when the fluid volume is sufficientlyreduced.
 2. The method of in claim 1, further comprising substantiallyisolating the thoracic duct from the venous system using the device suchthat flow from the thoracic duct is directed through the tubular memberto drain fluid from the lymphatic system.
 3. The method of claim 1,wherein the distal end of the tubular member is introduced into thevenous system until the distal end is advanced into the thoracic duct.4. The method of claim 1, further comprising applying negative pressureto the lumen to increase fluid flow from the thoracic duct through thecannula.
 5. The method of claim 1, wherein the device comprises asubcutaneous access port coupled to the tubular member for accessingfluid drained through the tubular member.
 6. The method of claim 1,wherein the device comprises one or more balloons on the tubular member,the method further comprising inflating the one or more balloons tomaintain the tubular member in a substantially fixed position relativeto the thoracic duct.
 7. The method of claim 1, wherein the devicecomprises a Nitinol frame, the method comprising expanding the frame tomaintain the tubular member in a substantially fixed position relativeto the thoracic duct.
 8. The method of claim 7, wherein the devicecomprises an elastic material on the Nitinol frame to substantiallyisolate the thoracic duct from the venous system and maintain thetubular member in a substantially fixed position relative to thethoracic duct.
 9. The method of claim 8, wherein the elastic materialcomprises silicone.
 10. The method of claim 1, further comprisingresuming draining fluid from the lymphatic system via the thoracic ductwhen the pressure in the thoracic duct exceeds a predeterminedthreshold.
 11. The method of claim 10, wherein the predeterminedthreshold is about twenty five millimeters of Mercury pressure (25 mmHg).
 12. A method for decreasing lymphocyte numbers in a patientaffected by autoimmune or infectious disease using a device comprising atubular member, the method comprising: placing a distal end of thetubular member into a patient's venous system such that the distal endis located adjacent the thoracic duct; draining fluid from the lymphaticsystem via the thoracic duct through a lumen of the tubular member. 13.The method of in claim 12, further comprising substantially isolatingthe thoracic duct from the venous system using the device such that flowfrom the thoracic duct is directed through the tubular member to drainfluid from the lymphatic system.
 14. The method of claim 12, wherein thedistal end of the tubular member is introduced into the venous systemuntil the distal end is advanced into the thoracic duct.
 15. The methodof claim 12, further comprising applying negative pressure to the lumento increase fluid flow from the thoracic duct through the cannula. 16.The method of claim 12, wherein the device comprises a subcutaneousaccess port coupled to the tubular member for accessing fluid drainedthrough the tubular member.
 17. The method of claim 12, wherein thedevice comprises one or more balloons on the tubular member, the methodfurther comprising inflating the one or more balloons to maintain thetubular member in a substantially fixed position relative to thethoracic duct.
 18. The method of claim 12, wherein the device comprisesa Nitinol frame, the method comprising expanding the frame to maintainthe tubular member in a substantially fixed position relative to thethoracic duct.
 19. The method of claim 18, wherein the device comprisesan elastic material on the Nitinol frame to substantially isolate thethoracic duct from the venous system and maintain the tubular member ina substantially fixed position relative to the thoracic duct.
 20. Themethod of claim 19, wherein the elastic material comprises silicone. 21.The method of claim 12, further comprising: analyzing lymphocytes in thefluid drained from the thoracic duct to identify a subset oflymphocytes; removing the identified subset of lymphocytes from thefluid; and returning the fluid into the patient's body after removingthe identified subset of lymphocytes.
 22. The method of claim 12,further comprising: analyzing lymphocytes in the fluid drained from thethoracic duct; processing the fluid outside the patient's body; andreturning the fluid into the patient's body.
 23. A method for evaluatinginterstitial fluid status within a patient's body, comprising: placing adistal end of a tubular member into a patient's venous system such thatthe distal end is located adjacent the thoracic duct; measuring pressurewithin the tubular member distal end to approximate lymphatic pressurewithin the thoracic duct; providing an alert outside the patient's bodywhen the measured pressure within the tubular member exceeds apredetermined threshold; and removing interstitial fluid from thethoracic duct via the tubular member until the measured pressure fallsbelow the predetermined threshold.
 24. A device for accessing fluid froma thoracic duct of a patient via the patient's venous system,comprising: a tubular member comprising a distal end sized forintroduction into the patient's venous system adjacent the thoracicduct; one or more features on the distal end for substantially isolatingthe thoracic duct from the venous system; and a lumen for withdrawinginterstitial fluid from the thoracic duct.
 25. The device of claim 24,wherein the one or more features comprise a Nitinol frame and a lowdurometer silicone component comprising an opening communicating withthe lumen.
 26. The device of claim 24, wherein the distal end is sizedto fit inside the subclavian vein of the patient, and wherein thetubular member has a length sufficient to extend to the thoracic ductfrom a percutaneous access point in the left subclavian vein.
 27. Thedevice of claim 25, wherein the Nitinol frame comprises two flexiblemembers extending from the tubular member and supporting the siliconecomponent.
 28. The device of claim 25, wherein the silicone component isbonded to the Nitinol frame, the silicone component being sufficientlyflexible to stretch to substantially seal the thoracic duct outlet.